Critical roles of NLRP3 inflammasome in IL-1beta secretion induced by Corynebacterium pseudotuberculosis in vitro.
Critical roles of NLRP3 inflammasome in IL-1beta secretion induced by Corynebacterium pseudotuberculosis in vitro.
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DOI：
10.1016/j.molimm.2019.09.016
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发表时间：
2019-12-01
影响因子：
3.6
通讯作者：
Fang, Rendong
中科院分区：
文献类型：
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作者：
Zhou, Zuoyong;Li, Hexian;Fang, Rendong
假结核棒状杆菌是引起人类和动物慢性炎症性疾病的主要病原体。白细胞介素-1 β（IL-1 β）参与对这些病原性感染的应答。然而，IL-1 β在C.假结核感染仍不清楚。本研究旨在探讨巨噬细胞感染C.假结核本研究首次揭示了核苷酸结合寡聚化结构域样受体家族、pyrin domain containing 3（NLRP 3）、凋亡相关斑点样蛋白（ASC）和caspase-1（Casp 1）在C.假结核感染的巨噬细胞Toll样受体4（TLR 4）部分参与C.假结核感染的巨噬细胞此外，核因子-κ B（NF-κ B）和p38丝裂原活化蛋白激酶（p38 MAPK）抑制剂几乎抑制了C细胞IL-1 β的分泌，提示NF-κ B和p38 MAPK通路参与了C细胞IL-1 β的分泌。假结核感染的巨噬细胞此外，C.在感染后24小时，Nlrp 3-/-、Asc-/-和Casp-1-/-巨噬细胞中的假结核杆菌的数量显著多于WT巨噬细胞（P < 0.05），表明NLRP 3炎性体组分限制了C.巨噬细胞中的假结核复制。总之，这些数据提供了新的见解，在C.假结核感染的巨噬细胞，并进一步了解目前的主机促炎性免疫反应对这种病原体。
Corynebacterium pseudotuberculosis is a prominent human and animal pathogen causing chronic inflammatory diseases. Interleukin-1beta (IL-1beta) is involved in the response to such pathogenic infections. However, the mechanism by which IL-1beta is secreted during C. pseudotuberculosis infection remains unclear. This study aimed to investigate the mechanism underlying IL-1beta secretion by macrophages infected with C. pseudotuberculosis. Herein, we firstly revealed that nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 (Casp1) play critical roles in IL-1beta secretion rather than IL-1beta precursor (pro-IL-1beta) expression in C. pseudotuberculosis-infected macrophages. Toll like receptor 4 (TLR4) is partially involved in IL-1beta secretion, while absent in melanoma 2 (AIM2) is not involved in IL-1beta secretion by C. pseudotuberculosis-infected macrophages. In addition, nuclear factor kappa B (NF-kappaB) and p38 mitogen-activated protein kinases (p38 MAPK) inhibitors almost attenuated IL-1beta secretion, implying that NF-kappaB and p38MAPK pathway are involved in IL-1beta secretion in C. pseudotuberculosis-infected macrophages. Furthermore, C. pseudotuberculosis were significantly more numerous in Nlrp3-/-, Asc-/-, and Casp-1-/- macrophages than in WT macrophages at 24 h after infection (P < 0.05), indicating that NLRP3 inflammasome components limit C. pseudotuberculosis replication in macrophages. Together, these data provide novel insights into the mechanisms underlying IL-1beta secretion in C. pseudotuberculosis-infected macrophages and further the current understanding of the host pro-inflammatory immune response against this pathogen.